INTRODUCTION:

Micro balloons are gastro-retentive drug delivery system (GRDDS) working on non-effervescent approach. Micro balloons are observed like spherical empty particles without core. These microballoons are characteristically free flowing powders which consist of proteins or synthetic polymers, ideally particle size should be less than 200μm. Gastro-retentive floating micro balloons is low density systems having sufficient buoyancy to float over gastric contents so that it remains in stomach for prolonged release period¹_.Glimepiride is an oral blood sugar-lowering drug. It is a second generation Sulfonylurea drug used for the management of Type-II diabetes mellitus. It is absorbed at the gastrointestinal tract. It has low biological half life (5 hrs), therefore it requires frequent administration. The dosing frequency should be reduced and patient compliance should be improved by prolonged release dosage forms.

Hence, there is a scope for continued interest and need for developing controlled release formulations².

MATERIALS AND METHODS:

Materials:

The Glimepiride (GMP) was supplied as a gift sample by USV chemicals, Lote. All other chemicals used were of analytical reagent grade.

Preparation of floating micro balloons:

Floating micro balloons containing Glimepiride were prepared by using emulsion solvent diffusion Technique. To prepare the different formulations, the drug to polymer ratio used was 1:6. The polymer content was a mixture of Eudragit RS 100 and hydroxypropyl methylcellulose. The drug polymer mixture was dissolved in a mixture (16 ml) of dichloromethane (DCM) and ethanol (1:1). The mixture was dropped in to 0.75% polyvinyl alcohol solution (200 ml) and the resulting solution was stirred with a magnetic stirrer at 300 rpm and 40°C for 1 h. The floating micro balloons formed were screened (#12), washed with water and dried at room temperature in desiccators³.

Table No. 1 Formulation Table

Formulation code	Glimepiride (gm)	Eudragit RS100 (gm)	HPMC (gm)
F1	0.1	0.6	0.0
F2	0.1	0.5	0.1
F3	0.1	0.4	0.2
F4	0.1	0.3	0.3
F5	0.1	0.2	0.4
F6	0.1	0.1	0.5
F7	0.1	0.0	0.6

Evaluation of prepared micro balloons:-

1. Percentage yield:

The percentage yield of different formulations was determined by weighing the hollow microspheres after drying. The percentage yield was calculated as follows:

2. Entrapment Efficiency:

Entrapment efficiency was determined by taking 20 mg of hollow micro balloons which were thoroughly triturated and dissolved with 10 ml ethanol in 100ml volumetric flask and volume Was made up with 0.1 N HCl. The resulting solution is then filtered (Whatman filter paper No. 44), suitably diluted and the absorbance was measured at 296nm against 0.1N HCI as blank. The percentage drug entrapment was calculated as follows.

3. Determination of tapped density, compressibility index and angle of repose

a) Tapp density:

Tapp density of hollow microballoons was determined by using the tapping method.

b) Compressibility index:

% Compressibility index where V and V0 are the volumes of the sample after and before the standard tapping respectively.

c) Angle of repose:

The angle of repose of hollow microballoons was determined by fixed funnel method.The angle of repose f was determined according to the following formula:

where, h = height of pile, r = radius of the pile

formed by the hollow microballoons⁴.

4. The study of drug release rates from floating glimepiride:

Floating behaviour:

Fifty milligrams of the floating microballoons were placed in simulated gastric fluid (pH 1.2, 100 ml) containing 0.02 w/v% Tween 20. The mixture was stirred at 100 rpm in a magnetic stirrer. After 6h, the floating and the settled portion of microballoons were recovered separately by filtration. The microballoons were dried and weighed. Both the fractions of microballoons were weighed and buoyancy was determined by the weight ratio of floating particles to the sum of floating and sinking particles.

where W_f and W_s are the weights of floating and settled microballoons respectively.

5. In-vitro release studies:

The in-vitro release of drug from the different formulations was examined using USP basket type dissolution apparatus. The amount of floating microballoons equivalent to 100 mg drug was placed in the basket. Simulated gastric fluid (pH 1.2) (900ml) was used as the dissolution medium and maintained at 37±0.5°C at a rotation speed of 100 rpm. An aliquot of 1 ml of the solution was withdrawn at predetermined time intervals and replaced by 1 ml of fresh dissolution medium. Samples were assayed spectrophotometrically at 249 nm after filtration through a 0.45 μm membrane filter (Millipore). The dissolution studies were repeated using phosphate buffer pH 7.4 as dissolution medium⁵.

RESULT AND DISCUSSION:

1. Percentage practical yield and Entrapment Efficiency:

All the formulations showed satisfactory entrapment efficiency ranging in 48.65 to 70.41% and with increasing the HPMC content its efficiency was slightly decreased.

Table No. 2 Percentage practical yield and %Entrapment Efficiency

Batch No.	% Practical yield	% Entrapment efficiency
F1	70.42	48.65
F2	75.32	55
F3	77.32	70.41
F4	76.31	56.32
F5	74.32	63.82
F6	72.69	68.41
F7	71.30	66.21

2. Tapped density, % Compressibility index, Angle of repose:

Density values for all formulations were less than that of gastric fluid (1.004 g/cm3), this indicates that they exhibit good buoyancy. All formulations showed excellent flowability as represented in the terms of angle of repose (<40°), tapped density (<1.21) and compressibility index (<19).

Table No. 3 Tapped density, % Compressibility index, Angle of repose

Batch No.	Tapped Density	% Compressibility index	Angle of Repose
F1	1.12±0.04	18.22±0.01	26.60±0.30
F2	1.15±0.07	15.72±0.08	27.32±0.15
F3	1.19±0.02	18.32±0.06	25.37±0.16
F4	1.12±0.04	16.54±0.04	26.36±0.13
F5	1.17±0.06	15.32±0.02	20.32±0.12
F6	1.11±0.03	13.37±0.06	18.37±0.14
F7	1.03±0.08	15.32±0.04	19.32±0.15

3. % Buoyancy study:

Buoyancy of the micro balloons decreased with increasing drug release. The floating ability pattern differed according to the formulation tested and medium used. F3 batch showed the best floating ability in 0.1 N HCl. Ideal properties of hollow micro balloons includes high buoyancy and sufficient release of drug in pH 7.4. Thus, F3 formulation showed appropriate buoyancy.

Table No. 4 % Buoyancy study

Batch No.	1hr	2hr	4hr	6hr
F1	98.55	94.02	91.39	90.28
F2	91.11	93.21	73.51	87.34
F3	98.41	97.08	93.23	91.47
F4	82.34	74.41	56.04	45.09
F5	98.39	85.60	65.14	57.76
F6	94.54	92.49	80.57	71.94
F7	95.21	81.34	60.76	42.31

4. In-vitro Drug Release:

F1, F2 formulations showed the % drug release as (79.42%, 63.21% respectively) in 12 h. The ratio of EudragitRS100 and HPMC was decreased and increased respectively to increase the % drug release rate. F4, F5 formulations showed low release rate (58.90%, 55.16%) in 10 h and F7, F8 formulations showed high release rate (95.21%, 93.81%) in 12 h, with less buoyancy. Drug release rate of F3 formulation was found to be 98.15% in 12 h, which is considered as a best formulation. 0.1 N HCl and phosphate buffer pH 7.4 were the dissolution medium used for evaluation of drug release rate. The drug release rate of F4 and F5 formulations were found to be slow and incomplete in both dissolution medium. It was found that drug release rate increased by decreasing and increasing the ratio of EudragitRS100 and HPMC respectively.

Table No. 5 In-vitro Drug Release

Batch No.	% Drug Release
Batch No.	1hr	2hr	3hr	4hr	5hr	6hr	7hr	8hr	9hr	10hr	11hr	12hr
F1	19.21	24.11	31.81	33.87	40.11	52.98	60.12	62.11	69.19	70.00	75.22	79.42
F2	21.32	25.45	31.02	35.76	38.40	41.67	45.54	54.43	54.36	56.71	60.24	63.21
F3	22.41	29.32	33.76	38.90	45.73	53.21	60.32	7532	75.67	82.11	90.56	98.15
F4	22.81	26.67	32.18	35.46	42.65	46.38	49.62	54.54	54.22	58.90	62.26	65.41
F5	19.00	25.12	29.56	32.28	34.39	39.58	43.55	52.16	52.21	55.16	61.33	66.31
F6	25.00	32.25	45.00	48.70	52.49	58.78	63.69	75.23	75.22	81.35	88.40	93.81
F7	15.09	29.22	32.51	43.09	51.08	57.51	67.11	72.57	79.39	82.51	90.20	95.21

Fig No. 1 In-vitro Drug Release